CRP and osteoprotegerin (OPG) roles for CVD and Stroke risks

A ssociation of plasma osteoprotegerin (OPG) and hsCRP to hospitalisation for ischaemic heart disease (IHD), ischaemic stroke and all-cause mortality, and the effect of combining plasma OPG and high-sensitivity C-reactive protein (hsCRP)

Heart disease and stroke are the leading causes of death worldwide. In 1997 Ridker et al reported on high-sensitivity C-reactive protein (hsCRP) being a strong predictor of future myocardial infarction and stroke. 
The novel risk factors are CRP, lipoprotein ( a) or Lp( a) , homocysteine , fibrinogen and myeloperoxidase ( MPO) , and enetic mutations and single – nucleotide polymorphisms in a number of candidate genes .

CRP has been shown to eb an independent risk factor for the development of cardiovascular events in both apparently healthy individuals and in patient with established coronary heart disease . Emerging evidences , indicates that CRP itself may have a direct causal influence on the development of atherosclerosis . CRP binds to oxidized LDL , promoting the uptake of LDL by macrophage scavenger cells in the arterial wall , and possibly enhancing the atherosclerotic process . 

AHA/centers for disease control and prevention (CDC) guideline have established cut-points of risk for hsCRP : a level of less than 1mg.L is considered low , 1 to 3 mg/l is average and more than 3 mg/L is high and associated with increased cardiovascular risk , higher levels ( >10mg/L) suggest an alternative cause for inflammation , such as infection or underlying rheumatologic illness.

Osteoprotegerin (OPG), a potential biomarker of atherosclerosis, is a glycoprotein that inhibits nuclear factor kappa B (NFκB)’s regulatory effects on inflammation, skeletal and vascular systems, and OPG seems to be involved in vascular calcification.Plasma OPG and hsCRP are both markers of inflammation and both proteins have been shown to be independent predictors of ischaemic stroke and heart disease.

Thus, plasma levels of OPG and hsCRP are reported to correlate only weakly to each other, and therefore may well represent different pathways of the atherosclerotic process

Plasma OPG has an inverse linear association with renal function. This association has been explained by either impaired renal clearance of OPG or by the fact that impaired renal function and atherosclerosis share some of the same pathogenic mechanisms, or it could be part of both. Nevertheless, finding of plasma OPG being associated to cardiovascular hospitalisation and all-cause mortality independently of GFR seems important.

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